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Commun Biol. 2020 Mar 19;3(1):133. doi: 10.1038/s42003-020-0802-y.

Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error.

Author information

1
Centre for Quantitative Medicine, Duke-NUS Medical School, 20 College Road, 169856, Singapore, Singapore. qiao.fan@duke-nus.edu.sg.
2
Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore. qiao.fan@duke-nus.edu.sg.
3
School of Optometry and Vision Sciences, Cardiff University, Cardiff, CF24 4HQ, UK.
4
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
5
Department of Statistical Science, School of Mathematics, Sun Yat-Sen University, Guangzhou, China.
6
Southern China Center for Statistical Science, Sun Yat-Sen University, Guangzhou, China.
7
Department of Ophthalmology, Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands.
8
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.
9
Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
10
Department of Ophthalmology and Visual Sciences, Kyoto University, Kyoto, 6068507, Japan.
11
Department of Epidemiology, Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands.
12
NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, EC1V 2PD, UK.
13
Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge, UK.
14
Ocular Epidemiology Research Group, Singapore Eye Research Institute, Singapore, Singapore.
15
QIMR Berghofer Medical Research Institute, Brisbane, Australia.
16
Department of Ophthalmology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131, Mainz, Germany.
17
Department of Ophthalmology, Inselspital, University Hospital Bern, University of Bern, Bern, 3010, Switzerland.
18
Saw Swee Hock School of Public Health, National University Health Systems, National University of Singapore, Singapore, Singapore.
19
Institute of Molecular Genetics, National Research Council of Italy, Pavia, 27100, Italy.
20
Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, FI-00290, Finland.
21
Department of Public Health, University of Helsinki, Helsinki, FI-00290, Finland.
22
Centre for Quantitative Medicine, Duke-NUS Medical School, 20 College Road, 169856, Singapore, Singapore.
23
Occupational and Environmental Health Sciences, School of Public Health and Preventative Medicine, Monash University, Melbourne, 3004, Australia.
24
Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, 3002, Australia.
25
Myopia Research Group, Singapore Eye Research Institute, Singapore, Singapore.
26
Beijing Institute of Ophthalmology, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
27
Department of Surgery, Ophthalmology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, 3002, Australia.
28
Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg-University Mainz, 55131, Mainz, Germany.
29
Dardenne Eye Hospital, Bonn-Bad Godesberg, Godesberg, 53117, Germany.
30
Centre for Ophthalmology and Visual Science, University of Western Australia, Lions Eye Institute, Perth, Australia.
31
School of Women's and Infants' Health, The University of Western Australia, Perth, WA, 6009, Australia.
32
School of Optometry, The Hong Kong Polytechnic University, Hong Kong SAR, China.
33
Orthoptics & Optometry, University of Applied Sciences, Utrecht, Netherlands.
34
Menzies Institute for Medical Research, School of Medicine, University of Tasmania, Hobart, Australia.
35
Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
36
Faculty of Medicine, University of Split, Croatia, Split, 21000, Croatia.
37
Section of Academic Ophthalmology, School of Life Course Sciences, King's College London, London, UK.
38
Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, USA.
39
Duke-NUS Medical School, Singapore, Singapore.
40
Centre for Vision Research, Department of Ophthalmology and Westmead Institute for Medical Research, University of Sydney, Sydney, NSW, 2145, Australia.
41
Gerontology Research Center and Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, FI-40100, Finland.
42
Department of Ophthalmology, Central Hospital of Central Finland, Jyväskylä, FI-40100, Finland.
43
San Giovanni di Dio hospital, Clinica Oculistica, Azienda Ospedaliera Universitaria di Cagliari, Cagliari, 09131, Italy.
44
Department of Surgical Sciences, Eye Clinic, University of Cagliari, Cagliari, 09131, Italy.
45
Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, China.
46
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, BS8 1NU, UK.
47
Department of Ophthalmology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
48
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China.
49
Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, VIC, Australia.
50
Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore.
51
Department Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.
52
Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore. cheng.ching.yu@seri.com.sg.
53
Ocular Epidemiology Research Group, Singapore Eye Research Institute, Singapore, Singapore. cheng.ching.yu@seri.com.sg.

Abstract

Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.

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